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Holding Abatacept Before Hip, Knee Surgery May Not Improve Outcomes
Withholding abatacept for 4 weeks or more prior to hip or knee replacement surgery did not lower the risk for infection among patients with rheumatoid arthritis, according to data published in Arthritis Care & Research.
“There is a great deal of ambiguity as to when someone on a biologic might need to hold or stop it ahead of elective surgery,” Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, told Healio Rheumatology. “The current recommendations that exist (eg, American College of Rheumatology) are based on very limited data that have some major limitations, mainly that they compare biologic users vs. nonusers. However, that is not really the right group of patients to study.”
Instead, Curtis and colleagues studied only those patients who were receiving IV abatacept (Orencia, Bristol Myers Squibb), and determined whether withholding the drug increased the risk for adverse outcomes by comparing various times that patients stopped prior to surgery with respect to serious infection, including prosthetic joint infection, he said. They accomplished this through a retrospective cohort study of U.S. Medicare and Truven MarketScan administrative data, from 2006 to September 2015.
The researchers focused on 1,780 adult patients with RA who received abatacept within 6 months of surgery. These patients accounted for 1,939 elective primary or revision hip or knee arthroplasties. Curtis and colleagues used propensity weighted analyses to compare the risk for 30-day hospitalized infection, as well as 1-year prosthetic joint infection, among patients who ceased abatacept at various times. In addition, secondary analyses evaluated nonurinary hospitalized infection and 30day readmission.
According to the researchers, there were 175 cases of hospitalized infection, 115 non-urinary hospitalized infections, 39 prosthetic joint infections and 114 30-day readmissions. The researchers found no significant differences between outcomes among patients who stopped abatacept less than 4 weeks prior to surgery compared with 4 to 8 weeks or more than 8 weeks. The ORs were 0.93 (95% CI, 0.651.34) for hospitalized infection, 0.93 (95% CI, 0.61.44) for nonurinary hospitalized infection and 1 (95% CI, 0.651.54) for 30-day readmission. The HR for prosthetic joint infection was 1.29 (95% CI, 0.622.69).
In addition, daily treatments of more than 7.5 mg of glucocorticoids were associated with a greater risk for hospitalized infection (OR = 2.19; 95% CI, 1.283.77) and nonurinary hospitalized infection (OR = 2.38; 95% CI, 1.224.64).
“This is clinically relevant because it implies that patients don’t need to be off RA biologics for prolonged periods of time before elective surgery,” Curtis said. “If they are off too long, they run the risk of flare of their RA, for which they are often given steroids, which increase infection risk and may impair wound healing.” – by Jason Laday
Disclosure: Curtis reports a research grant from Bristol-Myers Squibb, as well as consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, Myriad, Roche/Genentech, UCB, Amgen, Janssen, Pfizer and Corrona. Please see the study for all other relevant financial disclosures.
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This is an important study for practicing rheumatologists confronted with the decision of when to halt a biologic prior to knee or hip replacement. The ACR has published guidelines with the American Association of Hip and Knee Surgeons regarding the issue of when to stop conventional synthetic DMARDs prior to hip and knee replacements, concluding that DMARDs should be continued throughout the perioperative period.
In a prior retrospective study, the researchers had examined patients receiving infliximab in this joint replacement setting, whereas, in the current study, the researchers looked at nearly 2,000 elective joint replacement surgeries in 1,800 separate patients receiving chronic, stable biologic therapy with abatacept.
By using claims data from Medicare and MarketScan, the researchers were also able to track their two primary endpoints: Hospitalizations for serious infections within 30 days of surgery and prosthetic joint infections within 1 year of surgery. Further analysis of the data using ICD-9 diagnosis codes allowed them to determine the type of infection and length of hospitalization, as well as postoperative hospitalization.
The researchers found that dosing abatacept at <4 weeks was not a risk for infection or post-op hospitalization compared with longer dosing intervals preoperatively; in fact, the longer dosing intervals (4-8 weeks and >8 weeks) demonstrated a statistically longer postoperative hospitalization.
In the discussion, the researchers noted that there was a trend — albeit, not statistically significant and too small for separate analysis — for higher infections in the dosing of abatacept in the <2-week interval prior to surgery, which comprised 25% of short-dose interval patients. They also noted that this was for chronic, stable dosing of abatacept rather than for recent starts of abatacept, which may have a higher incidence of infection. In the discussion, the researchers state that it is reasonable to dose abatacept 2-4 weeks prior to surgery with no expectation of increased risk of infection.
Postoperatively, if the surgical site is healing well, the researchers note that abatacept can be resumed 14 days post-surgery, as addressed in ACR guidelines. Additional observations made in this study were that a prednisone dose >7.5 mg per day in the 90 days pre-surgery, compared with no glucocorticoids, was a significant risk factor for hospitalized infection and non-urinary hospitalized infection and a numerically greater risk of prosthetic joint infection, 30-day readmission and prolonged length of stay. Almost all of these risks were increased by a factor of 2 or more with a prednisone dose >7.5 mg/day.
One of the concerns, as a rheumatologist, is early withdrawal of biologic and/or DMARD therapy by the orthopedist, along with subsequent rheumatoid arthritis flare in the patient and the use of prednisone to control the flare. Although not shown in this study, the use of prednisone to control the flare may be more dangerous than just continuing therapy with the holding of biologics — in this case, abatacept — for as little as 2 weeks prior to the surgery.